Suppression of uterine insulin-like growth factor binding protein 5 by estrogen is mediated in part by insulin-like growth factor I.
Insulin-like growth factor I (IGF-I) is an important mediator of estradiol-induced uterine growth in vivo. Insulin-like growth factor binding proteins (IGFBPs) are known to regulate access of insulin-like growth factors to IGF receptors. In this report we demonstrate that the positive uterotrophic agent estradiol, suppresses expression of the IGFBP-5 gene in the uterus to less than 15% of control values, while oophorectomy results in uterine involution and is associated with a greater than 3-fold stimulation of uterine IGFBP-5 gene expression. Immunohistochemical studies show that in intact rat uterus, the luminal epithelial cells are weakly stained with IGFBP-5 antibodies. Following ovariectomy, IGFBP-5 is confined in the luminal epithelial layer and longidinal smooth muscle cells. Administration of estradiol to ovariectomized rats increases uterine weight and uterine IGF-I gene expression, while immunostaining of IGFBP-5 in the luminal epithelial cells and longidinal smooth muscle cells is almost extinguished. In vitro studies using primary uterine cells reveal that IGF-I increases thymidine incorporation and inhibits IGFBP-5 gene expression, whereas estradiol has no effect suggesting that in vivo estradiol-induced IGFBP-5 suppression is mediated through increased IGF-I production. Our results suggest that in vivo, the uterotrophic effects of estradiol are mediated at least in part by estradiol-stimulated uterine IGF-I expression which in turn inhibits IGFBP-5 expression, an action which would be expected to increase IGF bioactivity.
Huynh
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Lady Davis Research, Institute, McGill University, 3755 Cote Ste Catherine Road, Montreal, Quebec, H3T 1E2, Canada.
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013936:Thymidine